Guo Xiaodong, Jia Wenbo, Yang Xinyu, Jia Hexiao, Wu Hanyang, Wei Yihong, Can Can, He Na, Zhang Hailei, Liu Wancheng, Yu Shuang, Ma Daoxin
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China; Department of Hematology, Affiliated Hospital of Shandong University of traditional Chinese Medicine, Jinan 250012, Shandong, China.
Transl Oncol. 2025 Aug;58:102441. doi: 10.1016/j.tranon.2025.102441. Epub 2025 Jun 9.
Classical BCR-ABL-negative myeloproliferative neoplasms (MPNs) are a clonal expansion of myeloid precursors caused by somatic stem cells. Although driver mutations were observed in most MPN patients, the potential clonal disorder remains unclear. We analyzed a total of 1004 newly diagnosed MPN patients and next-generation sequencing was performed on the genomic DNA. Primary myelofibrosis (PMF) patients carried the highest LDH level, splenomegaly, and the lowest hemoglobin content. Myeloproliferative Neoplasm, unclassifiable (MPN-U) patients had higher platelet count and frequency of thrombotic events. The top five most frequently mutations were JAK2, ASXL1, TET2, CALR, and DNMT3A. The JAK2 mutation burden was positively correlated with leukocyte counts in all subgroups. PMF patients tend to have more somatic mutations than other patients. Among triple-negative (TN) MPN patients, SH2B3 and SRSF2 were positively correlated, and the NPM1 mutation rate was significantly increased. As for survival, we found that patients with PMF, MPN10 symptoms, JAK2 wild-type, or TN mutation were positively associated with shorter overall survival. The U2AF1 mutation was an independent risk factor for death in MPN patients, and ZRSR2, NF1, and PPM1D mutations were found in patients who progress to AML or MDS. In addition, we created a prediction nomogram by using five variables, which enhanced the precision of estimating survival in MPN patients. Our data provide a novel perspective for the diagnosis, clonal evolution and prognosis of MPNs.
经典的BCR-ABL阴性骨髓增殖性肿瘤（MPN）是由体细胞干细胞引起的髓系前体细胞的克隆性扩增。尽管在大多数MPN患者中观察到驱动突变，但潜在的克隆性疾病仍不清楚。我们共分析了1004例新诊断的MPN患者，并对基因组DNA进行了二代测序。原发性骨髓纤维化（PMF）患者的乳酸脱氢酶水平最高、脾肿大，血红蛋白含量最低。无法分类的骨髓增殖性肿瘤（MPN-U）患者的血小板计数和血栓形成事件发生率较高。最常见的前五个突变是JAK2、ASXL1、TET2、CALR和DNMT3A。JAK2突变负荷在所有亚组中均与白细胞计数呈正相关。PMF患者往往比其他患者有更多的体细胞突变。在三阴性（TN）MPN患者中，SH2B3和SRSF2呈正相关，NPM1突变率显著增加。关于生存情况，我们发现PMF、MPN10症状、JAK2野生型或TN突变的患者总生存期较短呈正相关。U2AF1突变是MPN患者死亡的独立危险因素，在进展为急性髓系白血病（AML）或骨髓增生异常综合征（MDS）的患者中发现了ZRSR2、NF1和PPM1D突变。此外，我们使用五个变量创建了一个预测列线图，提高了MPN患者生存估计的准确性。我们的数据为MPN的诊断、克隆进化和预后提供了新的视角。
